The PET method is a method in which a labeled compound that is labeled with a short-lived radioactive nucleus discharging positrons (hereinafter referred to as a “tracer”) is administered into a living body and the γ ray generated from this tracer is measured with a PET camera (detector constituted with a γ ray scintillator and a photoelectron multiplier) to thus image the distribution in the living body with a computer. This PET method is used in specification of a tumor site such as a cancer cell as a nuclear medicine examination, diagnosis of Alzheimer's disease, cerebral infarction and the like, diagnosis of mental diseases such as depression and evaluation of treatments, drug kinetics and evaluation of drugs.
Examples of short-lived radial nuclear species frequently used in the PET method include [11C] and [18F].
Among them, the tracer labeled with [11C] has an advantage of having an extremely wide applicable range because of utilizing a carbon atom present in all organic compounds. However, since the half-life period of [11C] is only about 20 minutes, it has been assumed that a labeling reaction by [11C] should be carried out within 40 minutes (within twice of the half-life period) until synthesis, purification, and administration into a living body. Regardless of such difficulties, the present inventors have developed rapid C-[11C]methylation reaction of various aromatic compounds and aryl compounds so far (for example, Patent Documents 1 and 2). The development enables a [11C]methylation reaction into the basic skeleton (in the carbon nucleus) of a compound due to a carbon-carbon bonding method. Therefore, as compared to a conventional [11C] methylation method on a hetero atom, it is expected that the labeled site is more stable for chemical and biological metabolism, and the method becomes a significantly powerful research means for drug discovery.
On the other hand, the half-life period of [18F] (110 minutes) is 5 time or more as compared to the half-life period of [11C] (20 minutes), and there is an advantage such that a time for preparation of a PET tracer and a time for PET diagnosis can be extended. In addition, when two PET tracers labeled with [11C] and [18F] to one desired compound can be realized, effective application of the difference of the half-life periods can be used as an extremely useful method for drug kinetics in a living body and an analysis of a metabolic product of the desired compound.
Therefore, the present inventors have developed a rapid C-[18F]fluoromethylation reaction of various aromatic compounds so far, in addition to development of the rapid C-[11C]methylation reaction (Patent Document 2). Patent Document 2 discloses that a coupling reaction of methyl fluoroiodide and a phenyl boronic acid pinacol ester progresses in a reaction time of only 5 minutes at a yield of 57%, as shown in the reaction formula below. This reaction can be classified as a kind of suzuki-miyaura cross coupling, and the coupling reaction is an innovative reaction from the viewpoint that SP3 carbon can be bonded to an aromatic ring.
